Hirschsprung's DiseasePhase 3Buty-HirschNCT03660176
Effects of Butyrate Enemas on Postoperative Intestinal Motility Disorders in Hirschsprung's Disease
A Phase 3 study testing Sodium Butyrate and routine management in people with Hirschsprung's Disease, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial summary
Hirschsprung's disease (HD) is a rare congenital disorder (1/5000) defined by the absence of ganglion cells in the submucosal and myenteric plexuses along a variable length of the digestive tract. This abnormality most often leads to distal bowel obstruction in newborns with delayed passage of meconium. Read more about this study
- Who is it for?
- Ages 7 days to 17 years
- Conditions the study is for
- Hirschsprung's Disease
- What is being tested?
- Sodium Butyrate and routine management
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2026to 2 May 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 days to 17 years
- All sexes
- No healthy volunteers
- Child
The inclusion criteria are:
- Newborn with a diagnosis of Hirschsprung's disease the 2 first months of life managed successfully with colonic decompressions/irrigations before curative surgery (usually performed 1-3 times a day)
- Born at or after 35 weeks of gestation (37 weeks of amenorrhea)
- With a short-segment Hirschsprung's disease limited to the rectum and/or sigmoid colon diagnosed on rectal biopsy with established pathological criteria (absence of ganglionic cells +/- hypertrophic extrinsic nerve fibres) (Kapur, 2009)
- Uncomplicated form (without enterocolitis as defined by the HAEC score and/or diverting colostomy)
- Curative surgery and follow-up in one of the included centres
- With consent of the 2 parents or legal(s) representative(s)
- Absence of severe or lethal associated malformations
- Affiliation with the French social security system
The non-inclusion criteria are:
- Long segment Hirschsprung's disease prior to the junction between the left colon and the sigmoid colon
- Hirschsprung's disease not managed successfully with colonic decompressions/irrigations and requiring a diverting colostomy before the curative surgery
- Hirschsprung-associated enterocolitis occurring before the randomization (as defined by the HAEC score)
- Severe or lethal associated malformation, including Down syndrome
- Intestinal associated malformations (intestinal atresia, gastroschisis, omphalocele, intestinal malrotation and volvulus)
- Any pathological condition that can modify intestinal motility or intestinal transit time (cystic fibrosis, hypothyroidism)
- Refusal of parent(s) or legal representative(s)
- Neonates under tutorship or guardianship Minors cannot be excluded because they are the population to be studied.
The non-inclusion criteria are:
- Long segment Hirschsprung's disease prior to the junction between the left colon and the sigmoid colon
- Hirschsprung's disease not managed successfully with colonic decompressions/irrigations and requiring a diverting colostomy before the curative surgery
- Hirschsprung-associated enterocolitis occurring before the randomization (as defined by the HAEC score)
- Severe or lethal associated malformation, including Down syndrome
- Intestinal associated malformations (intestinal atresia, gastroschisis, omphalocele, intestinal malrotation and volvulus)
- Any pathological condition that can modify intestinal motility or intestinal transit time (cystic fibrosis, hypothyroidism)
- Refusal of parent(s) or legal representative(s)
- Neonates under tutorship or guardianship Minors cannot be excluded because they are the population to be studied.
The non-inclusion criteria are:
- Long segment Hirschsprung's disease prior to the junction between the left colon and the sigmoid colon
- Hirschsprung's disease not managed successfully with colonic decompressions/irrigations and requiring a diverting colostomy before the curative surgery
- Hirschsprung-associated enterocolitis occurring before the randomization (as defined by the HAEC score)
- Severe or lethal associated malformation, including Down syndrome
- Intestinal associated malformations (intestinal atresia, gastroschisis, omphalocele, intestinal malrotation and volvulus).
- Any pathological condition that can modify intestinal motility or intestinal transit time (cystic fibrosis, hypothyroidism)
- Refusal of parent(s) or legal representative(s)
- Neonates under tutorship or guardianship Minors cannot be excluded because they are the population to be studied.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
Assistance Publique Des Hopitaux de Marseille
Marseille, PACA, 13354
About this study
Hirschsprung's disease (HD) is a rare congenital disorder (1/5000) defined by the absence of ganglion cells in the submucosal and myenteric plexuses along a variable length of the digestive tract. This abnormality most often leads to distal bowel obstruction in newborns with delayed passage of meconium. Treatment is surgical and consists in the resection of the aganglionic and transitional segments. However, the postoperative outcomes remain unpredictable. Despite complete curative surgery, intestinal functional disorders persist in 40-50% of children, mainly obstructive symptoms, and 15-25% of children will also develop postoperative enterocolitis, which remains the leading cause of mortality in HD. There is currently no preventive treatment of these intestinal functional disorders and enterocolitis. Recent preclinical studies have identified butyrate, a short-chain fatty acid, as a regulator of intestinal homeostasis in newborns and adults, particularly involved in maintaining epithelial integrity, regulating the immune response, and regulating the phenotype of the digestive tract and its functions. Butyrate regulates intestinal epithelial barrier functions by strengthening intestinal permeability, and regulates the functions of the enteric nervous system and its phenotype. In newborn rats, butyrate enemas increase the proportion of nitrergic (and also cholinergic) neurons, leading to improved nitrergic neurotransmission and, ultimately, improved colonic transit time.
Our main hypothesis is that recto-colonic butyrate enemas administered preoperatively in newborns and infants with HD should reduce postoperative functional intestinal motility disorders and enterocolitis in the short, medium, and long terms.
Read more
The BUTYHIRSCH project is a phase III, multicenter, national (24 pediatric surgery departments), controlled, randomized, open-label, prospective clinical drug trial. Fifty-eight patients will be included over a period of two years.
The primary objective is to determine the short-term efficacy of preoperative butyrate enemas in reducing the time to postoperative bowel recovery. The secondary objectives are to determine the medium- and long-term efficacy of preoperative butyrate enemas on 1) the incidence of postoperative obstructive functional symptoms, 2) the stool consistency, 3) the total postoperative intestinal transit time, 4) the incidence and severity of postoperative enterocolitis, and 5) the intestinal inflammation.
Patients will be randomized into 2 groups: the experimental group (29 patients) receiving a sodium butyrate recto-colic enema for 24 days before curative surgery and the control group (29 patients). Postoperative clinical follow-up will be prospective over 3 years in order to collect data on complications such as intestinal motility disorders and enterocolitis. No invasive or radiation-based examinations will be performed postoperatively. Additional investigative procedures will include assessment of total postoperative intestinal transit time using carmine red transit and assessment of intestinal inflammation by measuring fecal calprotectin.
examinations will be performed postoperatively. Additional investigative procedures will include assessment of total postoperative intestinal transit time using carmine red transit and assessment of intestinal inflammation by measuring fecal calprotectin.
- Conditions
- Hirschsprung's Disease
- Being tested
- Sodium Butyrate, routine management
- Keywords
- Hirschsprung disease, Congenital aganglionosis, Butyrate, Intestinal dysmotility
- Medical subject headings
- Hirschsprung Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium ButyrateDrug
Daily recto-colonic enemas of sodium butyrate (1.1 g/L solution, 10 mL/kg) administered for 24 days (±4 days) before curative surgery.
routine managementOther
Standard preoperative management for Hirschsprung's disease including colonic decompressions/irrigations before curative surgery.
| Study group | Role | What they receive |
|---|---|---|
| routine management | Active comparator | Participants receive routine preoperative management for Hirschsprung's disease before curative surgery, without butyrate enemas. Receives: Other: routine management |
| EXP GROUP | Experimental | Participants receive sodium butyrate recto-colonic enemas daily for 24 days before curative surgery in addition to routine preoperative management. Receives: Drug: Sodium Butyrate; Other: routine management |
What is being measured
The primary outcome is the main question the study is designed to answer.
The time to recovery of bowel function after the curative surgery. A 25% decrease of the time to recovery of bowel function in the experimental group as compared to the control group will be considered as clinically effective.
The recovery of bowel function is defined as follows:
- Tolerance of 2 feeds at full ration (as before surgery, breast-feeding or bottle-feeding),
- And passing stools.
The time to recovery of bowel function will be measured in hours from the end of the curative surgery.
Measured: Up to 30 days after surgery
Secondary outcomes (5)
Postoperative functional intestinal obstructive symptoms evaluated at each medical appointment
Functional intestinal obstructive symptoms are ongoing severe constipation, abdominal distension, bloating/soiling with or without foul-smelling stools/diarrhoea, functional bowel obstruction without bowel movements, after exclusion of surgical complications.
Measured: 3-4, 5, 6, 9, 12, 18, 24 and 36 months of life
The stool consistency evaluated using the validated 'Bristol' stool form scale modified for children at each medical appointment.
The stool consistency is evaluated using the 'Bristol' stool form scale modified for children. Stool consistency is correlated with total gastrointestinal transit time in children (Russo et al., 2013). The 'Bristol' stool form scale evaluates the stool consistency and is a six-point scale: 3 and 4 are considered as normal stool consistency and reflect a normal gastrointestinal transit time.
Measured: 3-4, 5, 6, 9, 12, 18, 24 and 36 months of life
The red carmine total intestinal transit time
The red carmine total transit time is an easy, non-invasive, and reproducible method to measure the total transit time in infants. This test consists in the per os administration of the dye (red carmine) by the parents at home. The capsule containing 250mg of red carmine will be opened and the red carmine powder will be mixed with milk (breast milk or formula) or mixed with food. The capsules of red carmine 250 mg will be prepared according to the French ANSM Formulaire National (see appendix). Capsules will be individually packaged in airtight, UV-protected blister packs labelled with the qualitative and quantitative composition. This preparation and the distribution will be realized by the Sponsor according to applicable regulation and Good Practices.
Measured: 1 month after surgery, 6 months of life (after diversification), 18 months of life and 36 months of life.
HAEC episode(s) defined by the HAEC score (Pastor et al., 2009; Frykman et al., 2017) and grading of HAEC (Gosain et al, 2017).
HAEC is defined by the HAEC score, a standardized definition for HAEC using clinical, biological, and radiological criteria The most important diagnostic criteria for HAEC were identified from a larger pool of potential diagnostic items through a consensus approach using the Delphi method (Pastor et al., 2009). A HAEC score of 10 or greater was initially chosen to indicate a diagnosis of HAEC, but the cut-off of 10 was not validated in clinical study at that time. Recently, the HAEC score was revised in a multicenter study (Frykman et al., 2017). A HAEC score of 4 maximized the sum of sensitivity (84%) and specificity (98.6%) while the previously cut-off of 10 showed lower sensitivity (42%) with perfect specificity. Grading of HAEC will be also established, from grade I (possible HAEC) to grade III (severe). Grading defines the guidelines for HAEC management (Gosain et al, 2017).
Measured: From surgery up to 3 years postoperatively
The fecal calprotectin
The fecal calprotectin concentrations will be measured using an enzyme-linked immunosorbent assay (ELISA). The stool samples will be sent to the laboratory of biochemistry of the Assistance Publique-Hôpitaux de Marseille where the procedure will be performed.
The fecal calprotectin is an established biomarker of acute and chronic gut inflammation. However, the fecal calprotectin concentrations have never been studied in HD infants. In necrotizing enterocolitis in premature newborns, current evidence suggests that fecal calprotectin is elevated but its significance as an early screening marker remains unknown and specific cut-off values are needed (Pergialiotis et al., 2016).
Measured: at the time of curative surgery, 1 month after surgery (2-3 months of life) and 6 months of life (after diversification)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2018
- Study startNov 2026 (estimated)
- Primary completion2 May 2031 (estimated)
- Study completion2 May 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hirschsprung's DiseaseStudies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, controlled, open-label, parallel-group, multicenter phase III study comparing preoperative sodium butyrate enemas plus routine management versus routine management alone.
- Masking
- None (open label)
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03660176
- Sponsor's protocol ID
- 2025-523094-42-00
- Other IDs
- 2025
- Acronym
- Buty-Hirsch
- Status last verified
- Sep 2026
- First submitted
- 4 Sep 2018
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Butyrate Enemas on Postoperative Intestinal Motility Disorders in Hirschsprung's Disease
- ClinicalTrials.gov ID
- NCT03660176
- Acronym / sponsor ID
- Buty-Hirsch / 2025-523094-42-00
- Conditions
- Hirschsprung's Disease
- Keywords
- Hirschsprung disease, Congenital aganglionosis, Butyrate, Intestinal dysmotility
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- Nov 2026 (estimated)
- Primary completion
- 2 May 2031 (estimated)
- Study completion
- 2 May 2031 (estimated)
- First posted
- 6 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hirschsprung's disease (HD) is a rare congenital disorder (1/5000) defined by the absence of ganglion cells in the submucosal and myenteric plexuses along a variable length of the digestive tract. This abnormality most often leads to distal bowel obstruction in newborns with delayed passage of meconium. Treatment is surgical and consists in the resection of the aganglionic and transitional segments. However, the postoperative outcomes remain unpredictable. Despite complete curative surgery, intestinal functional disorders persist in 40-50% of children, mainly obstructive symptoms, and 15-25% of children will also develop postoperative enterocolitis, which remains the leading cause of mortality in HD. There is currently no preventive treatment of these intestinal functional disorders and enterocolitis. Recent preclinical studies have identified butyrate, a short-chain fatty acid, as a regulator of intestinal homeostasis in newborns and adults, particularly involved in maintaining epithelial integrity, regulating the immune response, and regulating the phenotype of the digestive tract and its functions. Butyrate regulates intestinal epithelial barrier functions by strengthening intestinal permeability, and regulates the functions of the enteric nervous system and its phenotype. In newborn rats, butyrate enemas increase the proportion of nitrergic (and also cholinergic) neurons, leading to improved nitrergic neurotransmission and, ultimately, improved colonic transit time.
Our main hypothesis is that recto-colonic butyrate enemas administered preoperatively in newborns and infants with HD should reduce postoperative functional intestinal motility disorders and enterocolitis in the short, medium, and long terms.
The BUTYHIRSCH project is a phase III, multicenter, national (24 pediatric surgery departments), controlled, randomized, open-label, prospective clinical drug trial. Fifty-eight patients will be included over a period of two years.
The primary objective is to determine the short-term efficacy of preoperative butyrate enemas in reducing the time to postoperative bowel recovery. The secondary objectives are to determine the medium- and long-term efficacy of preoperative butyrate enemas on 1) the incidence of postoperative obstructive functional symptoms, 2) the stool consistency, 3) the total postoperative intestinal transit time, 4) the incidence and severity of postoperative enterocolitis, and 5) the intestinal inflammation.
Patients will be randomized into 2 groups: the experimental group (29 patients) receiving a sodium butyrate recto-colic enema for 24 days before curative surgery and the control group (29 patients). Postoperative clinical follow-up will be prospective over 3 years in order to collect data on complications such as intestinal motility disorders and enterocolitis. No invasive or radiation-based examinations will be performed postoperatively. Additional investigative procedures will include assessment of total postoperative intestinal transit time using carmine red transit and assessment of intestinal inflammation by measuring fecal calprotectin.
examinations will be performed postoperatively. Additional investigative procedures will include assessment of total postoperative intestinal transit time using carmine red transit and assessment of intestinal inflammation by measuring fecal calprotectin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized, controlled, open-label, parallel-group, multicenter phase III study comparing preoperative sodium butyrate enemas plus routine management versus routine management alone.
| Arm | Type | Receives |
|---|---|---|
| routine management | Active comparator | Other: routine managementParticipants receive routine preoperative management for Hirschsprung's disease before curative surgery, without butyrate enemas. |
| EXP GROUP | Experimental | Drug: Sodium Butyrate, Other: routine managementParticipants receive sodium butyrate recto-colonic enemas daily for 24 days before curative surgery in addition to routine preoperative management. |
Who may qualify
- Ages
- 7 days to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium ButyrateDaily recto-colonic enemas of sodium butyrate (1.1 g/L solution, 10 mL/kg) administered for 24 days (±4 days) before curative surgery. | Drug | EXP GROUP |
| routine managementStandard preoperative management for Hirschsprung's disease including colonic decompressions/irrigations before curative surgery. | Other | EXP GROUP, routine management |
Primary outcome
The time to recovery of bowel function after the curative surgery. A 25% decrease of the time to recovery of bowel function in the experimental group as compared to the control group will be considered as clinically effective.
Time frame: Up to 30 days after surgery
The recovery of bowel function is defined as follows: * Tolerance of 2 feeds at full ration (as before surgery, breast-feeding or bottle-feeding), * And passing stools. The time to recovery of bowel function will be measured in hours from the end of the curative surgery.
5 secondary outcomes
Postoperative functional intestinal obstructive symptoms evaluated at each medical appointment
Time frame: 3-4, 5, 6, 9, 12, 18, 24 and 36 months of life
The stool consistency evaluated using the validated 'Bristol' stool form scale modified for children at each medical appointment.
Time frame: 3-4, 5, 6, 9, 12, 18, 24 and 36 months of life
The red carmine total intestinal transit time
Time frame: 1 month after surgery, 6 months of life (after diversification), 18 months of life and 36 months of life.
HAEC episode(s) defined by the HAEC score (Pastor et al., 2009; Frykman et al., 2017) and grading of HAEC (Gosain et al, 2017).
Time frame: From surgery up to 3 years postoperatively
The fecal calprotectin
Time frame: at the time of curative surgery, 1 month after surgery (2-3 months of life) and 6 months of life (after diversification)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sodium Butyrate and routine management in people with Hirschsprung's Disease, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact ANNE DARIEL, MD (+33 491964885, Anne.DARIEL@ap-hm.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The time to recovery of bowel function after the curative surgery. A 25% decrease of the time to recovery of bowel function in the experimental group as compared to the control group will be considered as clinically effective. (time frame: Up to 30 days after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026.